In general, the present invention features methods of treating, reducing, or preventing autoimmune conditions, such as rheumatoid arthritis. Also disclosed are screening methods for identifying candidate compounds useful to treat, reduce, or prevent autoimmune conditions.
The immune system protects the body from potentially harmful agents such as microorganisms, cancer cells, and toxins. The body's ability to recognize foreign or ‘non-self’ entities or antigens results in the production of antibodies and in the sensitization of immune cells, ultimately culminating in the destruction of foreign agents.
Immune system disorders or autoimmune conditions arise when the immune system no longer differentiates self and non-self antigens and aberrantly mounts an immune response against self-antigens, thereby resulting in the destruction of host cells, tissues, or organs. Rheumatoid arthritis (RA) is one such disease, characterized by the slow erosion of the cartilage and bones. A large proportion of arthritic patients run a course of intermittent relapses and remissions with an overall pattern of slowly progressive joint destruction and deformity. Clinical manifestations include symmetrical polyarthritis of peripheral joints associated with pain, tenderness, swelling, and loss of function of affected joints; morning stiffness; loss of cartilage; erosion of bone matter; and subluxation of joints after persistent inflammation. This condition also manifests itself extra-articularly, causing rheumatoid nodules, rheumatoid vasculitis, pleuro-pulmonary inflammation, scleritis, sicca syndrome, Felty's syndrome (splenomegaly and neutropenia), osteoporosis, and weight loss (Katz Am. J. Med., (1985) 79:24 and Krane and Simon, Advances in Rheumatology, Synderman (ed.), (1986) 70(2):263-284). In some cases, arthritis may even be associated with mortality.
Autoimmune conditions are typically chronic in nature, requiring lifelong care and monitoring. Currently, most available treatment modalities are suboptimal and few autoimmune diseases can actually be cured. Medications or therapies that slow or suppress the immune system response in an attempt to halt the inflammation associated with the autoimmune response are often used. Unfortunately, these medications also suppress the ability of the immune system to fight infection and are therefore associated with various serious side effects. In the case of RA, various therapeutic strategies, including the administration of NSAIDs for example, may temporarily relieve arthritic symptoms. These strategies however, are often associated with limited efficacy and serious debilitating side effects.
Thus, better treatment modalities are required to treat, prevent, or reduce autoimmune conditions.